Abstract
Adult neurogenesis in mammals is restricted to some brain regions, in contrast with other vertebrates in which the genesis of new neurons is more widespread in different areas of the nervous system. In the mammalian cerebellum, neurogenesis is thought to be limited to the early postnatal period, coinciding with end of the granule cell genesis and disappearance of the external granule cell layer (EGL). We recently showed that in the rabbit cerebellum the EGL is replaced by a proliferative layer called ‘subpial layer’ (SPL) which persists beyond puberty on the cerebellar surface. Here we investigated what happens in the cerebellar cortex of peripuberal rabbits by using endogenous and exogenously-administered cell proliferation antigens in association with a cohort of typical markers for neurogenesis. We show that cortical cell progenitors extensively continue to be generated herein. Surprisingly, this neurogenic process continues to a lesser extent in the adult, even in the absence of a proliferative SPL. We describe two populations of newly generated cells, involving neuronal cells and multipolar, glia-like cells. The genesis of neuronal precursors is restricted to the molecular layer, giving rise to cells immunoreactive for GABA, and for the transcription factor Pax2, a marker for GABAergic cerebellar interneuronal precursors of neuroepithelial origin that ascend through the white matter during early postnatal development. The multipolar cells are Map5+, contain Olig2 and Sox2 transcription factors, and are detectable in all cerebellar layers. Some dividing Sox2+ cells are Bergmann glia cells. All the cortical newly generated cells are independent from the SPL and from granule cell genesis, the latter ending before puberty. This study reveals that adult cerebellar neurogenesis can exist in some mammals. Since rabbits have a longer lifespan than rodents, the protracted neurogenesis within its cerebellar parenchyma could be a suitable model for studying adult nervous tissue permissiveness in mammals.
Highlights
The cerebellum of non-mammalian vertebrates, such as fish, is characterized by striking neurogenesis throughout life [1]
Animals analysed in the present study will be referred to as postnatal when a typical external granule layer (EGL) is present in the cerebellum, peripuberal when a subpial layer (SPL) is detectable on the cerebellar surface, and adult (1–3 years old rabbits, devoid of cerebellar SPL)
In order to visualize the morphology of these cells, we employed antibodies raised against markers of structural plasticity, namely the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) and the collapsin response mediator protein-4 (CRMP-4) (Figure 1)
Summary
The cerebellum of non-mammalian vertebrates, such as fish, is characterized by striking neurogenesis throughout life [1]. The mammalian cerebellum after the early postnatal genesis of granule cells is known as one of the most static structures in the central nervous system (CNS) under the profile of cell renewal. Purkinje neurons and interneurons originate from the neuroepithelium of the fourth ventricle whereas granule cells come from actively proliferating cell precursors which accumulate in the external granule layer (EGL) after tangential migration from the rhombic lip [2]. The external granule layer (EGL) persists after birth on the cerebellar surface until it provides the granule cell population by radial migration during early postnatal periods whose duration is strictly dependent on the species [3,4,5,6]. All neuroepithelium-derived, GABAergic interneurons, including basket, stellate, and Golgi II cell precursors are produced by a common pool of progenitors [7] and express the paired box transcription factor Pax2 [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
